1. Field of the Invention
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This invention has relation to the use of an electrical treatment signal adapted for application to living animal tissue, including human tissue, to thereby induce electric current flow through cells of that tissue for the purpose of increasing the metabolic activity of the cells, and for the purpose of preventing further damage to cells in an area where cells have been initially damaged.
2. Description of the Prior Art
A chemiosmotic hypothesis has been promulgated by Peter D. Mitchell, Ph.D. Although Dr. Mitchell published a large number of papers in the scientific literature, an elucidation of this hypothesis, his life's work, was presented by him in THE NINTH CIBA MEDAL LECTURE and was published as follows: "Vectorial Chemistry and the Molecular Mechanics of Chemiosmotic Coupling: Power Transmission by Proticity." Biochemical Society Transactions, 1976, Vol. 4: Pgs. 400-430. To a substantial extent, this paper is an explanation of, an expansion of, and an updating of a paper published by him in 1966 entitled "Chemiosmotic Coupling in Oxidative and Photosynthetic Phosphorylation." Biological Review (1966), Vol. 41, Pgs. 445-502.
This hypothesis has now been widely accepted, and in 1976, Dr. Mitchell received the Nobel Prize for his work. The hypothesis was based on four fundamental postulates, as to the structural and functional systems involved in chemical and osmotic forces and by which proton-translocating mechanisms and proton-linked porter systems operate for cellular metabolism, through a topologically-closed insulating membrane, called the coupling membrane.
By translocating protons, a protonic potential differential is generated across the insulating membrane. This potential difference is quite similar to an electrical potential difference.
The chemiosmotic mechanism at the level of the cell membrane has sometimes been referred to as "the Mitchell pump", but not so designated by Dr. Mitchell.
Following the teachings of Dr. Mitchell, others have investigated the setting up of an electrical potential difference across areas of damaged epidermal and dermal tissue to study the effects of the flow of electrical currents through such tissue on the stimulation of metabolic activity. This includes the stimulation of the generation of adenosine triphosphate (ATP), protein synthesis, an accelerated cell membrane transport system, and an increase in the production of collagen.
Ngok Cheng, M.D. and his associates investigated some of these effects and published a paper entitled "The Effects of Electric Current on ATP Generation, Protein Synthesis and Membrane Transport in Rat Skin." Clinical Orthopedics 1982; Vol. 171, Pgs. 264-272.
Dr. Cheng and his colleagues reported some of the biochemical effects that occur in skin tissue of rats during in vitro stimulation with an electric current. Their method included the application of a direct electrical current to samples of tissue using currents that varied from one to 30,000 microamperes, usually for two to four hours at a constant temperature of 37.degree. C. Separate strips of living rat skin were exposed for 2 hours to 10, 50 , 100, 500, 1000 and 5000 microamperes direct current. These were then analyzed for ATP levels and compared with untreated (control) tissues. Their results indicated a five fold increase in ATP in tissue stimulated with 500 microamperes direct current.
Using one to 30,000 microamperes direct current to additional strips of rat tissue optimum incorporation of glycine into amino-acids, and subsequent synthesis of cell protein, occurred also at about 500 microamperes. Both ATP and protein synthesis fell off in a linear manner for tissue stimulated with 1000 to 5000 microamperes. At 5000 to 30,000 microamperes, protein synthesis did not occur, which findings suggested severe and/or lethal damage to the cells.
Oscar M. Alvarez, Ph.D. and his colleagues published a paper entitled: "The Healing of Superficial Skin Wounds is Stimulated by External Electrical Current." Journal of Investigative Dermatology, 1983; Vol. 81, Pgs. 144-148. Reported in this paper were the effects of direct electric current supplied by an energized silver-coated electrode on dermal and epidermal wound healing. Eleven young "Yorkshire" pigs were wounded, and a direct current was delivered by a silver-coated electrode directly over each wound through a wet dressing with the return electrode situated on another portion of the pig's body. A self-contained, battery-operated generator was a source of "constant current." The current was applied as steady state direct current for 24 hours at a time over a seven day term. During each 24 hour period, "the current intensity decreased linearly from 300 microamperes upon initial connection to 50 microamperes at the end of a 24 hour treatment period." A large increase in "labeled collagen" was noticed but not until four and five days after wounding.
Other work in the prior art is discussed in each of the foregoing papers, and is listed in the bibliography of each of these four papers.
A paper by J. J. Konikoff entitled: "Electrical Promotion of Soft Tissue Repairs"; Annals of Biomedical Engineering, Vol. 4, Pgs. 1-5 (1976) reported on the tensile strength of excised skin/incisions in rabbits that had been cut, and subjected to a 20 microampere current flow through the incisions for seven days. This current flow was direct and applied, apparently, without change of direction for the entire seven day test. Favorable results were obtained as to the strength of the treated skin/incisions compared to the untreated (control) incisions.
Other related papers, apparently also dealing with direct current applied over extended time period include the following: Wolcott, L. E. et al "Accelerated Healing of Skin Ulcers by Electrotherapy: Preliminary Clinical Results", Southern Medical Journal, Vol. 62, Pgs. 795-801 and bibliography cited therein.
This paper by Wolcott et al, after summarizing the problems faced in connection with bedsores or decubitus ulcers and other ischemic skin ulcers, goes on to characterize the state of the art prior to the present invention quite accurately as follows: "Historically, remedies have been distinguished by their ingenuity, variety and rather uniform ineffectiveness."
The literature relating to transcutaneous electrical nerve stimulation (TENS) and related to chronic ulcers of the skin has been consulted for possible pertinence to the present invention, and nothing pertinent has been located. For example, a book entitled: "Clinical Transcutaneous Electrical Nerve Stimulation" by Mannheimer and Lampe, has been published by F. A. Davis Company of Philadelphia, .COPYRGT.1984. It shows the present state of the art in the TENS field to be the use of spiked waveform electrical energy "bursts" of sufficient magnitude and duration to cause muscle twitching and contractions. The currents involved are several orders of magnitude greater than the currents utilized in the present invention.
A book "Chronic Ulcers of the Skin" by Y. Lee Bok, published by McGraw-Hill Book Company, .COPYRGT.1985, does not even refer to electrical stimulation. Dr. Bok is a recognized authority in his field.
No reference in either book was found which appeared pertinent to the present invention.
A computerized search of the literature relating to this invention has been made; but turned up nothing any more pertinent than the prior art discussed above.
As is evident from the above references, medical techniques for treating soft living animal tissue through the application of electrical energy have only recently been studied. All of the studies to date appear to use a unidirectional current flow. There are, however, detrimental side effects associated with this technique. Galvanic effects associated with unidirectional current flow can, for example, cause cell damage and loss of tissue integrity.
There is clearly a continuing need for improved medical techniques for treating such tissue. Electrical techniques appear to hold great promise. Improvements to known techniques which significantly increase treatment results would be especially desirable. Such techniques should employ current flows which do not have other adverse effects on living animal (including human) tissues, the cells which make up such tissues, or other biologic systems. To be avoided are current flows causing stress-electricity (piezoelectricity), excessive heat (pyroelectricity), electrical polarization, electrical double layering, or electrophoresis (field differential).
The instrument used to implement these techniques must, of course, be safe to use. The instrument should also be easy for clinicians to operate.
The inventors and those in privity with them are now aware of no prior art which is closer than that set out above; and are aware of no prior art which negates the patentability of the claims made herein.